This invention relates to a method of treating cancer.
The compound 5,6-dimethylanthenone-4-acetic acid PMAA) is known to have significant antitumour activity against murine turmous and human turmours xenografted in immunodeficient mice. Studies have shown that this activity is largely, if not entirely, a consequence of inhibition of blood flow selectively within tumours. However, to date, DMXAA has shown little evidence of clinically viable anti-cancer activity in humans.
The applicants have now surprisingly found that simultaneous or sequential administration of both a compound of the xanthenone acetic acid class (of which DMXAA is one) and either paclitaxel or docetaxel (both compounds of the taxane class of anticancer agents) results in an increase in antitumour activity such that the anticancer effect of the combination is much larger than for either agent alone, and greatly exceeds the sum of effects of the individual agents.
With this background in mind, it was an object of the present invention to provide a method of treatment of cancer which will at least provide the public with a useful choice.
Accordingly, in a first aspect, the present invention provides a method of treating cancer, the method comprising the step of administering to a mammal in need of such treatment, either simultaneously or sequentially, (i) a compound selected from paclitaxel and docetaxel, and (ii) a compound of the formula 
or a pharmaceutically acceptable salt or ester thereof,
wherein R1, R2 and R3 are each independently selected from the group consisting of H. C1xe2x80x94C6 alkyl, halogen, CF3, CN, NO2, NH2, OH, OR, NHCOR, NHSO2R, SR, SO2R or NHR, wherein each R is independently C1xe2x80x94C6 alkyl optionally substituted with one or more substituents selected from hydroxy, amino and methoxy, and wherein each of R1, R2 and R3 may be present at any of the available positions 1 to 8;
and wherein in each of the carbocyclic aromatic rings in formula (I), up to two of the methine (xe2x88x92CH=) groups may be replaced by an aza (xe2x88x92N=) group;
and wherein any two of R1, R2 and R3 may additionally together represent the group xe2x80x94CHxe2x95x90CHxe2x80x94CHxe2x95x90CHxe2x80x94, such that this group, together with the carbon or nitrogen atoms to which it is attached, forms a fused 6 membered aromatic ring.
Preferably, the mammal is a human.
Preferably, the compound of formula (I) is of the formula: 
Most preferably, the compound of formula (I) is 5,6-dimethylxanthenone-4-acetic acid, having the formula 
In a further aspect, the present invention provides the use of a compound of the formula (I) as defined above, or a pharmaceutically acceptable salt or ester thereof, in the manufacture of a medicament for treating cancer in a mammal by sequential or simultaneous co-administration of the medicament and a compound selected from paclitaxel and docetaxel.
In still a further aspect, the present invention provides the use of a compound selected from docetaxel and paclitaxel in the manufacture of a medicament for treating cancer in a mammal by sequential or simultaneous co-administration of the medicament and a compound of the formula (I) as defined above or a pharmaceutically acceptable salt or ester thereof.
In yet a further aspect, the present invention provides a pharmaceutical composition suitable for treating cancer, comprising a compound of the formula (I) as defined above or a pharmaceutically acceptable salt or ester thereof, and a compound selected from paclitaxel and docetaxel, in combination with one or more pharmaceutically acceptable carriers or vehicles.